Peptoid oligomers

Fig. 1.1 Comparison of the primary structure of peptide and peptoid oligomers...

The well-defined helical structure associated with appropriately substituted peptoid oligomers (Section 1.6) can be employed to fashion compounds that closely mimic the stracture and function of certain bioactive peptides. There are many examples of small helical peptides (<100 residues) whose mimicry by non-natural ohgomers could potentially yield valuable therapeutic and bioactive compounds. This section describes peptoids that have been rationaUy designed as mimics of antibacterial peptides, lung surfactant proteins, and coUagen proteins. Mimics of HIV-Tat protein, although relevant to this discussion, were described previously in this chapter (Sections 1.3.2 and 1.4.1). 

Initial studies on short peptoid oligomers have revealed relatively poor pharmacokinetic properties [18, 79]. Despite the numerous advantageous attributes of peptoids in vitro, there are currently no peptoid-based therapeutics. However, a more thorough exploration of peptoid sequences may reveal species with more appropri-... 

Burkoth, T. S., Faearman, A.T., Char-YCH, D. H., Connolly, M.D., and Zuckermann, R.N. Incorporation of unprotected heterocyclic side chains into peptoid oligomers via solid-phase submonomer synthesis. J. Am. Chem. Soc. 2003 125, 8841-8845. 

Wu, C.W., Sanborn, T.J., Zuckermann, R.N., and Barron, A. E. Peptoid oligomers with alpha-chiral, aromatic side chains Effects of chain length on secondary structure. /. Am. Chem. Soc. 2001, 723, 2958-2963. 

The only published X-ray diffraction structure for any peptoid oligomer, the Nrch (8) homo-pentamer, shows clearly that the molecule is folded in a left-handed helical conformation with... 

In early 1998, a further class of peptoid oligomers appeared [25], when a solid-phase method was developed to synthesize N-substituted P-aminopropionic acid oligomers, termed P-peptoids. Treatment of Wang s resin with acryloyl chloride, followed by Michael addition of primary amines afforded N-substituted P-alanines. A combinatorial library of... 

Peptoid oligomers are synthesized on a Rink amide resin (50 /Ltmol scale) to avoid diketopiperazine formation. In order to suppress the formation of diketopiperazine during the synthesis of peptoids with a C-terminal carboxylic group, one can use the 2-chloro tritylchloride resin [155]. Following Fmoc removal, the resin is bromoacylated by successively adding a solution of bromoacetic acid (83 mg, 600 tmol, 12 equiv.) in DMF (830 fiL) and 200 fiL of DIG (103 /xL, 660 tmol, 13 equiv.) in DMF (170 >L) to the resin. The reaction mixture is shaken for 30 min at room temperature. A double coupling is performed systematically. The resin is then filtered and washed three times with 2 mL of DMF. The nucleophilic substitution step... 

Peptoid Oligomers Peptidomimetics for Diverse Biomedical Applications... 

Peptoid Oligomers PepUdomimelics for Diverse Biomedical ApplicaBons 275... 

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A comparison of linear and cyclic peptoid oligomers as potent antimicrobial agents. ChemMedChem 7 114-122... 

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